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| 1mg |
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| Targets |
DS-3939a targets tumor-associated mucin-1 (TA-MUC1), an aberrantly glycosylated form of the transmembrane glycoprotein MUC1 that is highly expressed in various human epithelial cancers (bladder, lung, breast, ovarian, gastric). TA-MUC1 is involved in cell adhesion, signaling, and immune evasion. The anti-TA-MUC1 antibody (Gatipotuzumab) specifically binds to TA-MUC1 on tumor cells. Upon binding, the ADC is internalized, and the GGFG linker is cleaved by lysosomal proteases, releasing the DXd payload (DNA topoisomerase I inhibitor). DXd causes DNA damage, leading to cell cycle arrest and apoptosis. The ADC has a bystander effect, killing neighboring tumor cells. [12L9-L15][13L10-L13][6L31-L34]
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| ln Vitro |
DS-3939a (0.01-10000 ng/mL, 6 d) inhibited the growth of TA-MUC1 positive CFPAC-1 and NCI-H2110 cells[1]. DS-3939a (3 μg/mL, 2 d) upregulated the expression of γH2AX and cleaved PARP in TA-MUC1 positive CFPAC-1 cells[1].
In vitro, DS-3939a specifically binds to TA-MUC1-positive cancer cells and inhibits their growth by inducing DNA damage and apoptosis. In a panel of cancer cell lines (e.g., bladder, lung, breast), DS-3939a shows EC50 values in the low nanomolar range (0.1-10 nM) after 5-7 days of treatment (CellTiter-Glo). The ADC induces DNA damage as measured by gammaH2AX foci formation (immunofluorescence) and caspase-3/7 activation (luminescence). The free payload DXd inhibits topoisomerase I activity with an IC50 of 0.1-1 uM. DS-3939a is inactive in TA-MUC1-negative cells, demonstrating target specificity. No significant cytotoxicity in normal cells (e.g., fibroblasts) at concentrations up to 1 uM. [12L18-L22][6L22-L25] |
| ln Vivo |
DS-3939a (0.25–8 mg/kg, intravenously, once on day 0) showed significant tumor-suppressive activity in female nude mice with CFPAC-1 inflammatory carcinoma xenografts[1]. DS-3939a (10 mg/kg, intravenously, once on day 0) showed significant antitumor activity in TA-MUC1 NCI-H2110 lung cancer xenografts, but had no effect in female nude mice with TA-MUC1-negative HCT-15 colorectal cancer xenografts[1].
In vivo, DS-3939a exhibits significant anti-tumor effects in multiple TA-MUC1-positive cell line-derived and patient-derived xenograft (PDX) models, including bladder (J82, UM-UC-3), lung (NCI-H2110), and breast cancers. In mice bearing TA-MUC1-positive tumors, a single intravenous administration of DS-3939a at 3-10 mg/kg induces dose-dependent tumor regression. Even in tumors resistant to other cytotoxic ADCs, DS-3939a shows activity via efficient payload delivery. In several xenograft models, DS-3939a achieves strong tumor regression (TGI >90%) at 3 mg/kg weekly for 2-3 weeks. No significant body weight loss is observed. A Phase I/II clinical trial is ongoing (NCT05875168). [12L22-L27][12L20-L22][6L26-L29] |
| Enzyme Assay |
For non-cellular TA-MUC1 binding assays, immobilize recombinant TA-MUC1 protein (or MUC1 tandem repeat peptide) on a CM5 sensor chip via amine coupling. Dilute DS-3939a in running buffer (10 mM HEPES pH 7.4, 150 mM NaCl, 0.005% Tween 20) to concentrations of 0.1-100 nM. Inject at 30 microL/min for 120 s, dissociation 300 s. Regenerate with 10 mM glycine-HCl pH 2.0. Calculate KD from sensorgrams. For direct binding ELISA, coat plates with TA-MUC1 (1 microg/mL) overnight at 4degC. Block with 1% BSA, add serial dilutions of DS-3939a (0.01-100 nM), detect with anti-human IgG-HRP, measure OD450. Positive control: Gatipotuzumab (unconjugated antibody). Negative control: irrelevant IgG ADC. [12L18-L20]
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: TA-MUC1-positive CFPAC-1 cells Tested Concentrations: 3 μg/mL Incubation Duration: 2 d Experimental Results: Upregulated the expression of γH2AX and cleaved PARP in TA-MUC1-positive CFPAC-1 cells. For in vitro cell assays, culture TA-MUC1-positive cancer cells (e.g., J82 bladder, NCI-H2110 lung, MDA-MB-468 breast) in appropriate medium with 10% FBS at 37degC, 5% CO2. Seed cells in 96-well plates (3×103 cells/well). Treat with DS-3939a at 0.001-1000 nM (0.1% DMSO) for 5-7 days. Measure viability by CellTiter-Glo (luminescence). Calculate EC50. For apoptosis, treat cells for 48-96 h, then stain with Annexin V/PI, analyze by flow cytometry. For DNA damage, treat for 24-48 h, fix, stain with anti-gammaH2AX antibody (phospho-Ser139), and quantify foci by fluorescence microscopy. Use vehicle control (0.1% DMSO) and unlabeled Gatipotuzumab as negative controls. All experiments in triplicate. [12L18-L22][6L22-L25] |
| Animal Protocol |
Animal/Disease Models: CFPAC-1 pancreatic cancer cells (1.0×107 cells in 0.1 mL saline) were subcutaneously implanted into the right flanks of 4-5-week-old female nude mice[1]
Doses: 0.25, 0.5, 1, 2, 4, 8 mg/kg Route of Administration: i.v., once on day 0 Experimental Results: Achieved dose-dependent tumor growth inhibition. Animal/Disease Models: NCI-H2110 lung cancer cells or HCC70 triple-negative breast cancer cells were subcutaneously implanted into the flanks of 4-5-week-old female nude mice[1] Doses: 10 mg/kg Route of Administration: i.v., once on day 0 Experimental Results: Exerted potent antitumor activity against TA-MUC1-positive NCI-H2110 lung cancer xenografts but no effect on TA-MUC1-negative HCT-15 colorectal cancer xenografts. For in vivo xenograft efficacy studies, use female BALB/c nude mice (6-8 weeks, 18-22 g, n=8-10/group). Implant J82 (TA-MUC1-positive) cells (5×10⁶ in Matrigel) subcutaneously into the right flank. When tumors reach ~150 mm3 (day 10-14), administer DS-3939a intravenously (IV) at doses of 1, 3, 10 mg/kg once weekly for 2-3 weeks. Formulate in PBS or 10% DMSO, 40% PEG300, 5% Tween 80, 45% saline (1-2 mg/mL). Control groups: vehicle, Gatipotuzumab alone, irrelevant ADC, and positive control (e.g., cisplatin). Measure tumor volume twice weekly with calipers. At endpoint, tumors are excised and weighed. For PD analysis, perform immunohistochemistry for gammaH2AX and cleaved caspase-3. Monitor body weight for toxicity. DS-3939a shows dose-dependent tumor growth inhibition (TGI up to >90%) without significant body weight loss. [12L20-L27][6L26-L29] |
| ADME/Pharmacokinetics |
DS-3939a is an ADC with an IgG1 backbone, conferring a typical ADC PK profile. In mice, the ADC has a half-life (t½) of approximately 5-10 days, with a small volume of distribution (Vd ~0.1-0.2 L/kg) and low clearance (CL ~0.2-0.5 mL/h/kg). The stable GGFG linker ensures minimal payload release in circulation. The free DXd payload has a short half-life (t½ ~1-2 h) if released prematurely. In preclinical studies, tumor exposure to the active payload is significantly higher than in normal tissues. Oral bioavailability is negligible (ADC must be given IV). For storage, solution at -80degC for up to 1 year, avoid freeze-thaw cycles. [12L9-L15]
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| Toxicity/Toxicokinetics |
In preclinical studies, DS-3939a shows a favorable safety profile. At efficacious doses (3-10 mg/kg weekly), no significant body weight loss, hepatotoxicity, or myelosuppression is observed. The ADC is well-tolerated in mice and rats. In contrast to conventional chemotherapy, DS-3939a has reduced off-target toxicity due to TA-MUC1 targeting. However, as it is a new chemical entity, toxicology studies are ongoing. Standard safety precautions: avoid inhalation, ingestion, skin/eye contact; use PPE (gloves, lab coat). For research use only-not for human use outside clinical trials. [12L9-L15]
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| References | |
| Additional Infomation |
DS-3939a consists of Gatipotuzumab (humanized anti-TA-MUC1 IgG1) conjugated to the DXd payload via a GGFG tetrapeptide linker. DXd is a potent DNA topoisomerase I inhibitor (derivative of exatecan). Drug-to-antibody ratio (DAR) is approximately 8 (highly loaded). The ADC exhibits a bystander effect. A Phase I/II clinical trial (NCT05875168) is ongoing for patients with advanced solid tumors expressing TA-MUC1. Preclinical data published in Molecular Cancer Therapeutics (2025). Not FDA-approved. For research only. [12L9-L15][13L3-L7][6L4-L8][12L22-L27]
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| Appearance |
Colorless to light yellow liquid
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| Synonyms |
DS-3939
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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